No Adaptation of the Prion Strain in a Heterozygous Case of Variant Creutzfeldt-Jakob Disease - Volume 26, Number 6—June 2020 - Emerging Infectious Diseases journal - CDC

No Adaptation of the Prion Strain in a Heterozygous Case of Variant Creutzfeldt-Jakob Disease - Volume 26, Number 6—June 2020 - Emerging Infectious Diseases journal - CDC

Volume 26, Number 6—June 2020

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No Adaptation of the Prion Strain in a Heterozygous Case of Variant Creutzfeldt-Jakob Disease

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Aileen Boyle, Chris Plinston, Fraser Laing, Graeme Mackenzie, Robert G. Will, Jean C. Manson, and Abigail B. Diack 

Author affiliations: The Roslin Institute, Easter Bush, Scotland, UK (A. Boyle, C. Plinston, F. Laing, A.B. Diack); Western General Hospital, Edinburgh, Scotland, UK (G. Mackenzie); University of Edinburgh, Edinburgh (R.G. Will, J.C. Manson)

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Abstract

We investigated a clinical case of variant Creutzfeldt-Jakob Disease in a person heterozygous for methionine/valine at codon 129 of the prion protein gene and identified the same strain properties in variant Creutzfeldt-Jakob disease in methionine homozygous persons and in bovine spongiform encephalopathy. These results indicate no adaptation of the agent in a different genetic background.

In 2016, a definite case of clinical variant Creutzfeldt-Jakob disease (vCJD) in a person heterozygous for methionine/valine (MV) at codon 129 of the prion protein gene (PRNP 129MV) was reported in the United Kingdom (1). Given the relatively atypical clinical features in this case, we considered it important to ascertain the strain of prion agent to determine whether there had been strain adaption or whether the patient’s genetic background may have influenced the disease phenotype. We conducted a study to determine whether we could isolate the same prion strain from this case of vCJD in a 129MV individual as was identified in previous 129 methionine homozygous (129MM) genotype vCJD cases, consistent with the hypothesis of a causal link to bovine spongiform encephalopathy (BSE).

The clinical features for this patient were consistent with a diagnosis of either vCJD or sporadic Creutzfeldt-Jakob disease (sCJD). Results from magnetic resonance imaging (MRI) of the patient’s brain were suggestive of sCJD on diffusion-weighted imaging (DWI) sequences, although the single coronal fluid-attenuated inversion recovery (FLAIR) sequence in this case was not diagnostic because of movement artifact. Results of cerebrospinal fluid (CSF) real-time quaking-induced conversion assay analysis and the direct detection assay for vCJD infection in the blood were negative. However, at autopsy, neuropathological examination revealed florid plaques, and biochemical analysis of prion protein (PrP) from the brain confirmed a type 2B profile, both characteristic of vCJD (1). Abnormal PrP was also detected in peripheral tissues. Recent studies in which researchers used protein misfolding cyclic amplification in CSF were positive in this case of vCJD, but not in sCJD cases, including those with a heterozygous genotype (2).